基于分子对接技术虚拟筛选延胡索抗心肌缺血物质基础研究
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摘要
目的研究延胡索抗心肌缺血的物质基础及作用机制。方法通过TCMSP平台筛选到符合条件的目标小分子化合物,运用Maesrto11.1分子对接软件筛选延胡索中与相应靶点蛋白对接较好的小分子化合物,再运用Cytoscape3.6.1构建多成分-靶点网络药理图,通过拓扑学分析,阐释其网络特征。结果在16种心肌缺血靶点对接结果中,8种季铵碱化合物、1种黄酮类、2种叔胺碱类显示出了较好的对接结果。季铵碱类化合物和黄酮类槲皮素对接结果普遍优于叔胺碱类,对接结果中季铵碱打分平均值高于叔胺碱的靶点蛋白有10种。网络药理学结果分析得知多化合物-靶点的网络异质性为0.57,平均相邻节点数3.59,特征网络长度3.02,网络中心度0.21。结论延胡索季铵碱类化合物黄连碱、巴马汀、去氢紫堇鳞茎碱、药根碱、非洲防己碱、小檗碱,黄酮类槲皮素可能是其治疗心肌缺血的物质基础,延胡索治疗心肌缺血是多成分与多靶点相互作用的结果。
Objective To study the material basis and mechanism of Corydalis Rhizoma in the treatment of myocardial ischemia by using molecular docking technology. Methods In this paper, the target small molecule compounds were screened by TCMSP platform, and Maesrto11.1 software was used to dock the small molecule compounds in Corydalis Rhizoma with the corresponding target protein. Cytoscape 3.6.1 was used to construct multi-component-target network pharmacology figure, and its network characteristics was elucidated by topology analysis. Results Among the 16 myocardial ischemia-related targets, 8 quaternary amine, 1 flavonoid, and 2 tertiary amine bases showed good docking results. The docking results of quaternary amine compounds and flavonoids were generally better than those of tertiary amines. In the docking results, there were 10 kinds of target protein in the quaternary amine base with higher quaternary amine base than tertiary amine base. The results of network pharmacology analysis showed that the network heterogeneity was 0.57, the average number of adjacent nodes was 3.59, the characteristic network length was 3.02, and the network centrality was 0.21. Conclusion Corydalis Rhizoma quaternary amine compounds such as coptisine, palmatine,dehydrocorybulbine, jatrorrhizine, columbamine, berberine, and quercetin may be the material basis for the treatment of myocardial ischemia. Corydalis Rhizoma treatment of myocardial ischemia is the result of the interaction between multi-component and multi-target.
Objective To study the material basis and mechanism of Corydalis Rhizoma in the treatment of myocardial ischemia by using molecular docking technology. Methods In this paper, the target small molecule compounds were screened by TCMSP platform, and Maesrto11.1 software was used to dock the small molecule compounds in Corydalis Rhizoma with the corresponding target protein. Cytoscape 3.6.1 was used to construct multi-component-target network pharmacology figure, and its network characteristics was elucidated by topology analysis. Results Among the 16 myocardial ischemia-related targets, 8 quaternary amine, 1 flavonoid, and 2 tertiary amine bases showed good docking results. The docking results of quaternary amine compounds and flavonoids were generally better than those of tertiary amines. In the docking results, there were 10 kinds of target protein in the quaternary amine base with higher quaternary amine base than tertiary amine base. The results of network pharmacology analysis showed that the network heterogeneity was 0.57, the average number of adjacent nodes was 3.59, the characteristic network length was 3.02, and the network centrality was 0.21. Conclusion Corydalis Rhizoma quaternary amine compounds such as coptisine, palmatine,dehydrocorybulbine, jatrorrhizine, columbamine, berberine, and quercetin may be the material basis for the treatment of myocardial ischemia. Corydalis Rhizoma treatment of myocardial ischemia is the result of the interaction between multi-component and multi-target.
引文
[1]中国药典[S].一部.2015.
[2]程星烨.延胡索抗心肌缺血活性部位物质基础研究[D].北京:中国协和医科大学中国医学科学院,2008.
[3]李秋月.延胡索生物碱谱效关系及相互作用研究[D].北京:中国协和医科大学中国医学科学院,2014.
[4]李克宁,郑惠婷,王淑美,等.基于分子对接技术虚拟筛选葛根治疗脑卒中的物质基础研究[J].中草药,2018,49(8):1847-1853.
[5]潘婷婷,周植星,韩英梅,等.基于植物成分的蛋白酶激活受体1拮抗剂的虚拟筛选和实验筛选[J].中草药,2014,45(10):1427-1433.
[6]汝锦龙.中药系统药理学数据库和分析平台的构建和应用[D].咸阳:西北农林科技大学,2015.
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[13]董亚楠,韩彦琪,张铁军,等.基于网络药理学的六经头痛片治疗偏头痛的作用机制探讨[J].中草药,2017,48(20):4174-4180.
[14]李小龙.灯盏花素的心肌保护作用及其机制研究[D].杭州:浙江大学,2004.
[15]史春志.大蒜素对大鼠心肌细胞缺氧/复氧、缺血/再灌注损伤保护作用及其机制研究[D].武汉:华中科技大学,2006.
[16]Gong L L,Fang L H,Du G H,et al.Coptisine exert cardioprotective effect through anti-oxidative and inhibition of Rho A/Rho kinase pathway on isoproterenol-induced myocardial infarction in rat[J].Atherosclerosis,2012,222(1):50-58.
[17]Yao Q,Xu D,Li H L,et al.Berberine promoted myocardial protection of postoperative patients through regulating myocardial autophagy[J].Biomed Pharmacother,2018,105(1):1050-1053.
[18]Kim Y M,Ha Y M,Jin Y C,et al.Palmatine from Coptidis rhizoma reduces ischemia reperfusion-mediated acute myocardial injury in the rat[J].Food Chem Toxicol,2009,47(8):2097-2102.
[19]Luo T,Zhang H,Wang H Q,et al.Neuroprotective effect of Jatrorhizine on peroxide-indueced cell injury and its potential mechanisms in PC12 cells[J].Neurosci Lett,2011,498(3):227-231.
[20]Badr R,Hashemi M,Javadi G,et al.Assessment of global ischemic/reperfusion and Tacrolimus administration on CA1 region of hippocampus:Gene expression profiles of BAX and BCL2 genes[J].Bratisl Med J,2016,117(6):358-362.
[21]Dong L Y,Chen F,Xu M,et al.Quercetin attenuates myocardial ischemia-reperfusion injury via downregulation of the HMGB1-TLR4-NF-κB signaling pathway[J].AMJ Transl Res,2018,10(15):1273-1283.
[22]岳志杰,石展,杜昱蕾,等.L-型钙通道自身调控异常参与缺血再灌注心肌钙超载的形成[J].生理学报,2017,69(6):861-869.
[2]程星烨.延胡索抗心肌缺血活性部位物质基础研究[D].北京:中国协和医科大学中国医学科学院,2008.
[3]李秋月.延胡索生物碱谱效关系及相互作用研究[D].北京:中国协和医科大学中国医学科学院,2014.
[4]李克宁,郑惠婷,王淑美,等.基于分子对接技术虚拟筛选葛根治疗脑卒中的物质基础研究[J].中草药,2018,49(8):1847-1853.
[5]潘婷婷,周植星,韩英梅,等.基于植物成分的蛋白酶激活受体1拮抗剂的虚拟筛选和实验筛选[J].中草药,2014,45(10):1427-1433.
[6]汝锦龙.中药系统药理学数据库和分析平台的构建和应用[D].咸阳:西北农林科技大学,2015.
[7]Wu S,Chang G,Zhang D,et al.Trimetazidine protects against myocardial/reperfusion injury by inhibiting excessive autophagy[J].J Mol Med,2018,96(8):791-806.
[8]Deng Y L,Zhao J Y,Quan X Q,et al.Verpamil suppress cardiac alternans and ventricular arrhythmias in acute myocardial ischemia via ryanodine receptor inhibition[J].Am J Transl Res,2017,9(6):2712-2722.
[9]Wei Y,Meng T,Sun C,et al.Protect effect of diltiazem on myocardial ischemic rats induced by isoproterenol[J].Mol Med Rep,2018,17(1):495-501.
[10]Wishart D S,Knox C,Guo A C,et al.Drug Bank:Acomprehensive resource for in silico drug discovery and exploration[J].Nucleic Acids Res,2006,34(1):668-672.
[11]蒋芦荻,陈茜,张燕玲,等.基于分子对接技术的高频降脂药对作用机制研究[J].中国中药杂志,2015,40(12):2413-2419.
[12]Sastry G M,Adzhiqirey M,Sherman W,et al.Prorein and ligand preparation parameters protocols and influence on virtual screening enrichments[J].J Comput Aided Mol Des,2013,27(3):221-234.
[13]董亚楠,韩彦琪,张铁军,等.基于网络药理学的六经头痛片治疗偏头痛的作用机制探讨[J].中草药,2017,48(20):4174-4180.
[14]李小龙.灯盏花素的心肌保护作用及其机制研究[D].杭州:浙江大学,2004.
[15]史春志.大蒜素对大鼠心肌细胞缺氧/复氧、缺血/再灌注损伤保护作用及其机制研究[D].武汉:华中科技大学,2006.
[16]Gong L L,Fang L H,Du G H,et al.Coptisine exert cardioprotective effect through anti-oxidative and inhibition of Rho A/Rho kinase pathway on isoproterenol-induced myocardial infarction in rat[J].Atherosclerosis,2012,222(1):50-58.
[17]Yao Q,Xu D,Li H L,et al.Berberine promoted myocardial protection of postoperative patients through regulating myocardial autophagy[J].Biomed Pharmacother,2018,105(1):1050-1053.
[18]Kim Y M,Ha Y M,Jin Y C,et al.Palmatine from Coptidis rhizoma reduces ischemia reperfusion-mediated acute myocardial injury in the rat[J].Food Chem Toxicol,2009,47(8):2097-2102.
[19]Luo T,Zhang H,Wang H Q,et al.Neuroprotective effect of Jatrorhizine on peroxide-indueced cell injury and its potential mechanisms in PC12 cells[J].Neurosci Lett,2011,498(3):227-231.
[20]Badr R,Hashemi M,Javadi G,et al.Assessment of global ischemic/reperfusion and Tacrolimus administration on CA1 region of hippocampus:Gene expression profiles of BAX and BCL2 genes[J].Bratisl Med J,2016,117(6):358-362.
[21]Dong L Y,Chen F,Xu M,et al.Quercetin attenuates myocardial ischemia-reperfusion injury via downregulation of the HMGB1-TLR4-NF-κB signaling pathway[J].AMJ Transl Res,2018,10(15):1273-1283.
[22]岳志杰,石展,杜昱蕾,等.L-型钙通道自身调控异常参与缺血再灌注心肌钙超载的形成[J].生理学报,2017,69(6):861-869.